The phenomenon of tolerance and physical dependence to opiates develops in the fetus in addited mothers. The recent finding that tolerance and dependence to morphine develops in the chick embryo opens the possibility of demonstrating the developmental stage at which tolerance and dependence to morphine can be produced in the embryo. Neurons in the chick embryonic CNS require thyroxine for differentiation, as in the fetal mammal. Antithyroid drugs, such as methimazole, delay neuronal differentiation in the developing organism by inhibiting the development of the thyroid gland. the role of neuronal differemtiation in the development of embryonic tolerance and dependence to morphine will be assessed by administration of methimazole in graded doses to chick embryos prior to the administration of morphine. The hypothesis will be tested that methimazole blocks or delays the development of tolerance and dependence. Parallel studies to the chick embryo experiments will be carried out with rate fetuses.